EU/3/16/1613 - orphan designation for treatment of progressive supranuclear palsy

tolfenamic acid

Overview

On 17 February 2016, orphan designation (EU/3/16/1613) was granted by the European Commission to RV Developpement, France, for tolfenamic acid for the treatment of progressive supranuclear palsy.

What is progressive supranuclear palsy?

Progressive supranuclear palsy, which is also known as Steele-Richardson-Olszewski syndrome, is a disease that involves the gradual deterioration of brain cells. Symptoms include loss of balance with unexplained falls, stiffness, difficulty moving the eyes, particularly up and down, personality changes and dementia (loss of intellectual function). The disease usually starts in people aged over 60 years and gradually gets worse over a number of years.

Patients with progressive supranuclear palsy have abnormal build-up and tangles of a protein called tau in their brain, which is thought to cause the deterioration of brain tissue in these patients.

Progressive supranuclear palsy is a debilitating and life-threatening disease that leads to parkinsonism, paralysis and premature death.

What is the estimated number of patients affected by the condition?

At the time of designation, progressive supranuclear palsy affected approximately 0.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 31,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

---

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 513,700,000 (Eurostat 2016).

What treatments are available?

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of progressive supranuclear palsy. Because of their tendency to fall, patients were often offered walking aids, as well as special glasses to help them to look down. Physiotherapy was used to keep the joints flexible. For patients unable to swallow, a feeding tube leading through the tummy to the stomach was used. Medicines developed to treat Parkinson's disease were also used in some patients, but their effect was usually limited, and did not last long.

How is this medicine expected to work?

Brain cells of patients with progressive supranuclear palsy produce excessive tau protein. In addition, the protein has extra phosphate groups attached to it which cause it to fold wrongly and become tangled. Tolfenamic acid interferes with Sp1, a factor that is essential for controlling the amount of tau protein that a cell makes and the processes that add phosphate groups to the protein. This combined effect is expected to reduce the production of tau protein and the development of tangles, and thereby prevent cell damage and symptoms of progressive supranuclear palsy.

What is the stage of development of this medicine?

The effects of tolfenamic acid have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with tolfenamic acid in patients with progressive supranuclear palsy had been started.

At the time of submission, tolfenamic acid was not authorised anywhere in the EU for progressive supranuclear palsy or designated as an orphan medicinal product elsewhere for this condition.

Tolfenamic acid has been authorised in Europe for many years as a non-steroidal anti-inflammatory medicine (NSAID) for the treatment of pain and inflammation.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 21 January 2016 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.

EU/3/16/1613: Public summary of opinion on orphan designation: Tolfenamic acid for the treatment of progressive supranuclear palsy

Adopted Reference Number: EMA/COMP/75475/2016

Key facts

• Active substance:
  tolfenamic acid
• Intended use:
  Treatment of progressive supranuclear palsy
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/16/1613
• Date of designation:
  17/02/2016
• Sponsor:

  RV Developpement; 5 Résidence des Prés; 57510 Puttelange-aux-Lacs; France; Tel. [phone]; E-mail: [e-mail]

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.